Abstract
Aims: The aim of the study was to investigate the antihyperglycemic effect of L-Tartaric acid.
Background: L-Tartaric acid is a natural product with possible beneficial effects on health.
Objective: The goal of this work was to evaluate the antihyperglycemic and antidyslipidemic effects of L-Tartaric acid (L-TA) in rats.
Materials and Methods: In the first model, the effects of L-TA (10 and 40 mg/kg) on diabetes conditions induced by streptozotocin (STZ) in rats were investigated. In the second model, the effects of L-TA (40 and 80 mg/kg) on dyslipidemia induced by tyloxapol (Triton WR-1339) in rats were assessed.
Results: L-TA (40 mg/kg) had improved all studied parameters. L-TA at 40 mg/kg was able to significantly reduce glycaemia, improve oral glucose tolerance (OGT), increase glycogen content in liver and extensor digitorum longus (EDL) muscle, and ameliorate the lipidic profile and atherogenic indices in STZ-diabetic rats.
Conclusion: L-Tartaric acid was able to exhibit antihyperglycemic and antidyslipidemic effects in STZ-induced diabetic rats. Moreover, the antidyslipidemic effect of L-Tartaric acid was confirmed in tyloxapol-induced hyperlipidemic rats.
Graphical Abstract
[1]
Popović-Djordjević, J.B.; Katanić Stanković, J.S.; Mihailović, V.; Pereira, A.G.; Garcia-Oliveira, P.; Prieto, M.A.; Simal-Gandara, J. Algae as a source of bioactive compounds to prevent the development of type 2 Diabetes Mellitus. Curr. Med. Chem., 2021, 28(23), 4592-4615.
[http://dx.doi.org/10.2174/0929867328666210325100654] [PMID: 33823760]
[http://dx.doi.org/10.2174/0929867328666210325100654] [PMID: 33823760]
[2]
Ikewuchi, J.C.; Ikewuchi, C.C.; Ifeanacho, M.O. Attenuation of salt-loading induced cardiomegaly and dyslipidemia in Wistar rats by aqueous leaf extract of Chromolaena odorata. Pharmacol. Pharm., 2014, 5(2), 160-170.
[http://dx.doi.org/10.4236/pp.2014.52022]
[http://dx.doi.org/10.4236/pp.2014.52022]
[3]
Goldberg, I.J. Clinical review 124: Diabetic dyslipidemia: Causes and consequences. J. Clin. Endocrinol. Metab., 2001, 86(3), 965-971.
[http://dx.doi.org/10.1210/jcem.86.3.7304] [PMID: 11238470]
[http://dx.doi.org/10.1210/jcem.86.3.7304] [PMID: 11238470]
[4]
de Sousa, J.A.; Pereira, P.; Allgayer, M.C.; Marroni, N.P.; de Barros Falcão Ferraz, A.; Picada, J.N. Evaluation of DNA damage in Wistar rat tissues with hyperlipidemia induced by tyloxapol. Exp. Mol. Pathol., 2017, 103(1), 51-55.
[http://dx.doi.org/10.1016/j.yexmp.2017.06.009] [PMID: 28684216]
[http://dx.doi.org/10.1016/j.yexmp.2017.06.009] [PMID: 28684216]
[5]
Schofield, J.D.; Liu, Y.; Rao-Balakrishna, P.; Malik, R.A.; Soran, H. Diabetes Dyslipidemia. Diabetes Ther., 2016, 7(2), 203-219.
[http://dx.doi.org/10.1007/s13300-016-0167-x] [PMID: 27056202]
[http://dx.doi.org/10.1007/s13300-016-0167-x] [PMID: 27056202]
[6]
Seedevi, P.; Ramu Ganesan, A.; Moovendhan, M.; Mohan, K.; Sivasankar, P.; Loganathan, S.; Vairamani, S.; Shanmugam, A. Anti-diabetic activity of crude polysaccharide and rhamnose-enriched polysaccharide from G. lithophila on Streptozotocin (STZ)-induced in Wistar rats. Sci. Rep., 2020, 10(1), 556.
[http://dx.doi.org/10.1038/s41598-020-57486-w] [PMID: 31953455]
[http://dx.doi.org/10.1038/s41598-020-57486-w] [PMID: 31953455]
[7]
Li, W.; Yuan, G.; Pan, Y.; Wang, C.; Chen, H. Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: A review. Front. Pharmacol., 2017, 8, 8-74.
[http://dx.doi.org/10.3389/fphar.2017.00074] [PMID: 28280467]
[http://dx.doi.org/10.3389/fphar.2017.00074] [PMID: 28280467]
[8]
Burbidge, C.A.; Ford, C.M.; Melino, V.J.; Wong, D.C.J.; Jia, Y.; Jenkins, C.L.D.; Soole, K.L.; Castellarin, S.D.; Darriet, P.; Rienth, M.; Bonghi, C.; Walker, R.P.; Famiani, F.; Sweetman, C. Biosynthesis and cellular functions of tartaric acid in grapevines. Front. Plant Sci., 2021, 12, 643024.
[http://dx.doi.org/10.3389/fpls.2021.643024] [PMID: 33747023]
[http://dx.doi.org/10.3389/fpls.2021.643024] [PMID: 33747023]
[9]
Derewenda, Z.S. On wine, chirality and crystallography. Acta Crystallogr. A, 2008, 64(1), 246-258.
[http://dx.doi.org/10.1107/S0108767307054293] [PMID: 18156689]
[http://dx.doi.org/10.1107/S0108767307054293] [PMID: 18156689]
[10]
Yan, X.; Qin, C.; Deng, D.; Yang, G.; Feng, J.; Lu, R.; Wang, G.; Nie, G. Regulation of glucose and lipid metabolism by insulin and glucagon in vivo and in vitro in common carp Cyprinus carpio L. Aquacult. Rep., 2020, 18(18), 100427.
[http://dx.doi.org/10.1016/j.aqrep.2020.100427]
[http://dx.doi.org/10.1016/j.aqrep.2020.100427]
[11]
Silva, M.M.; Lidon, F.C. An overview on applications and side effects of antioxidantfood additives. Emir. J. Food Agric., 2016, 823-832.
[12]
Coban, H.B. Organic acids as antimicrobial food agents: Applications and microbial productions. Bioprocess Biosyst. Eng., 2020, 43(4), 569-591.
[http://dx.doi.org/10.1007/s00449-019-02256-w] [PMID: 31758240]
[http://dx.doi.org/10.1007/s00449-019-02256-w] [PMID: 31758240]
[13]
Spiller, G.A.; Story, J.A.; Furumoto, E.J.; Chezem, J.C.; Spiller, M. Effect of tartaric acid and dietary fibre from sun-dried raisins on colonic function and on bile acid and volatile fatty acid excretion in healthy adults. Br. J. Nutr., 2003, 90(4), 803-807.
[http://dx.doi.org/10.1079/BJN2003966] [PMID: 13129449]
[http://dx.doi.org/10.1079/BJN2003966] [PMID: 13129449]
[14]
Anasuya, A.; Sasikala, M. Tartaric acid inhibits urinary stone formation in rats. Nutr. Res., 1989, 9(5), 575-580.
[http://dx.doi.org/10.1016/S0271-5317(89)80182-4]
[http://dx.doi.org/10.1016/S0271-5317(89)80182-4]
[15]
Bai, F.; Wang, Y.; Zhang, S.; Wang, Y.; Zhang, J.; Cao, J.; Sun, L. Caffeoyl substitution changes the inhibition mode of tartaric acid against α-amylase: Analysis of the enzyme inhibition by four caffeic and tartaric acid derivates. Lebensm. Wiss. Technol., 2020, 133, 109942.
[http://dx.doi.org/10.1016/j.lwt.2020.109942]
[http://dx.doi.org/10.1016/j.lwt.2020.109942]
[16]
OECD/OCDE. Guideline for the testing of chemicals. acute oral toxicity e acute toxic class method: Test no-423. Organisation for economic co-operation and development., 2001.
[17]
Schlede, E.; Genschow, E.; Spielmann, H.; Stropp, G.; Kayser, D. Oral acute toxic class method: A successful alternative to the oral LD50 test. Regul. Toxicol. Pharmacol., 2005, 42(1), 15-23.
[http://dx.doi.org/10.1016/j.yrtph.2004.12.006] [PMID: 15896439]
[http://dx.doi.org/10.1016/j.yrtph.2004.12.006] [PMID: 15896439]
[18]
Bello, I.; Bakkouri, A.; Tabana, Y.; Al-Hindi, B.; Al-Mansoub, M.; Mahmud, R.; Asmawi, M. Acute and sub-acute toxicity evaluation of the methanolic extract of Alstonia scholaris stem bark. Med. Sci., 2016, 4(1), 4.
[http://dx.doi.org/10.3390/medsci4010004] [PMID: 29083368]
[http://dx.doi.org/10.3390/medsci4010004] [PMID: 29083368]
[19]
Amssayef, A.; Eddouks, M. Acute toxicity analysis and antidiabetic effect of the Moroccan spider flower (Cleome Arabica L.) in normal and sreptozotocin-induced diabetic rats. Endocr. Metab. Immune Disord. Drug Targets, 2021, 21(8), 1423-1430.
[http://dx.doi.org/10.2174/1871530320666201007150438] [PMID: 33030136]
[http://dx.doi.org/10.2174/1871530320666201007150438] [PMID: 33030136]
[20]
Amssayef, A.; Azzaoui, B.E.; Ajebli, M.; Eddouks, M. Antidyslipidemic and antioxidant activities of Matricaria pubescens (Desf.) Shultz. in streptozotocin-induced diabetic rats. Cardiovasc. Hematol. Agents Med. Chem., 2021, 19(1), 62-71.
[http://dx.doi.org/10.2174/1871525718666200506100139] [PMID: 32370726]
[http://dx.doi.org/10.2174/1871525718666200506100139] [PMID: 32370726]
[21]
Amssayef, A.; Eddouks, M. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Cotula cinerea (Del) in normal and streptozotocin-induced diabetic rats. Endocr. Metab. Immune Disord. Drug Targets, 2020, 20(9), 1504-1513.
[http://dx.doi.org/10.2174/1871530320666200513081312] [PMID: 32400337]
[http://dx.doi.org/10.2174/1871530320666200513081312] [PMID: 32400337]
[22]
El-Ouady, F.; Amssayef, A.; Eddouks, M. Antihyperglycemic and antidyslipidemic activities of the aqueous Salvia hispanica extract in diabetic rat. Cardiovasc. Hematol. Agents Med. Chem., 2022, 20(1), 60-66.
[23]
Morris, S. The estimation of glycogen with anthrone reagent. Science, 1948, 107(2775), 254.
[http://dx.doi.org/10.1126/science.107.2775.254] [PMID: 17814729]
[http://dx.doi.org/10.1126/science.107.2775.254] [PMID: 17814729]
[24]
Carroll, N.V.; Longley, R.W.; Roe, J.H. The determination of glycogen in liver and muscle by use of anthrone reagent. J. Biol. Chem., 1956, 220(2), 583-593.
[http://dx.doi.org/10.1016/S0021-9258(18)65284-6] [PMID: 13331917]
[http://dx.doi.org/10.1016/S0021-9258(18)65284-6] [PMID: 13331917]
[25]
Ajebli, M.; Amssayef, A.; Eddouks, M. Antihyperglycemic activity and safety assessment of the aqueous extract of aerial parts of Scorzonera undulata ssp deliciosa in rat. Cardiovasc. Hematol. Disord. Drug Targets, 2021, 20(4), 305-316.
[http://dx.doi.org/10.2174/1871529X20666200827113029] [PMID: 32860366]
[http://dx.doi.org/10.2174/1871529X20666200827113029] [PMID: 32860366]
[26]
Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 1972, 18(6), 499-502.
[http://dx.doi.org/10.1093/clinchem/18.6.499] [PMID: 4337382]
[http://dx.doi.org/10.1093/clinchem/18.6.499] [PMID: 4337382]
[27]
Dobiášová, M.; Frohlich, J.; Šedová, M.; Cheung, M.C.; Brown, B.G. Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography. J. Lipid Res., 2011, 52(3), 566-571.
[http://dx.doi.org/10.1194/jlr.P011668] [PMID: 21224290]
[http://dx.doi.org/10.1194/jlr.P011668] [PMID: 21224290]
[28]
Amssayef, A.; Eddouks, M. Antidyslipidemic capacity of Cleome arabica (L.) in streptozotocin-induced diabetic rats. Cardiovasc. Hematol. Agents Med. Chem., 2022, 20(1), 52-59.
[29]
Xuan, J.; Feng, Y. Enantiomeric tartaric acid production using cis-epoxysuccinate hydrolase: History and perspectives. Molecules, 2019, 24(5), 903.
[http://dx.doi.org/10.3390/molecules24050903] [PMID: 30841503]
[http://dx.doi.org/10.3390/molecules24050903] [PMID: 30841503]
[30]
Salehi, B.; Iriti, M.; Vitalini, S.; Antolak, H.; Pawlikowska, E.; Kręgiel, D.; Sharifi-Rad, J.; Oyeleye, S.I.; Ademiluyi, A.O.; Czopek, K.; Staniak, M.; Custódio, L.; Coy-Barrera, E.; Segura-Carretero, A.; Cádiz-Gurrea, M.L.; Capasso, R.; Cho, W.C.; Seca, A.M.L. Euphorbia-derived natural products with potential for use in health maintenance. Biomolecules, 2019, 9(8), 337.
[http://dx.doi.org/10.3390/biom9080337] [PMID: 31382529]
[http://dx.doi.org/10.3390/biom9080337] [PMID: 31382529]
[31]
Locke, A.; Locke, R.B.; Schlesinger, H.; Carr, H. The comparative toxicity and cathartic efficiency of disodium tartrate and fumarate, and magnesium fumarate, for the mouse and rabbit. J. Am. Pharm. Assoc., 1942, 31(1), 12-14.
[http://dx.doi.org/10.1002/jps.3030310103]
[http://dx.doi.org/10.1002/jps.3030310103]
[32]
Lenzen, S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia, 2008, 51(2), 216-226.
[http://dx.doi.org/10.1007/s00125-007-0886-7] [PMID: 18087688]
[http://dx.doi.org/10.1007/s00125-007-0886-7] [PMID: 18087688]
[33]
Kakimoto, T.; Kimata, H.; Iwasaki, S.; Fukunari, A.; Utsumi, H. Automated recognition and quantification of pancreatic islets in Zucker diabetic fatty rats treated with exendin-4. J. Endocrinol., 2013, 216(1), 13-20.
[http://dx.doi.org/10.1530/JOE-12-0456] [PMID: 23092878]
[http://dx.doi.org/10.1530/JOE-12-0456] [PMID: 23092878]
[34]
Golson, M.L.; Maulis, M.F.; Dunn, J.C.; Poffenberger, G.; Schug, J.; Kaestner, K.H.; Gannon, M.A. Activated FoxM1 attenuates streptozotocin-mediated β-cell death. Mol. Endocrinol., 2014, 28(9), 1435-1447.
[http://dx.doi.org/10.1210/me.2014-1024] [PMID: 25073103]
[http://dx.doi.org/10.1210/me.2014-1024] [PMID: 25073103]
[35]
Eddouks, M.; Khallouki, F.; Owen, R.W.; Hebi, M.; Burcelin, R. Evaluation of glucose and lipid lowering activity of Arganimide A in normal and streptozotocin-induced diabetic rats. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(4), 503-510.
[http://dx.doi.org/10.2174/1871530318666181113124727] [PMID: 30421687]
[http://dx.doi.org/10.2174/1871530318666181113124727] [PMID: 30421687]
[36]
Eddouks, M.; Lemhadri, A.; Michel, J.B. Caraway and caper: Potential anti-hyperglycaemic plants in diabetic rats. J. Ethnopharmacol., 2004, 94(1), 143-148.
[http://dx.doi.org/10.1016/j.jep.2004.05.006] [PMID: 15261975]
[http://dx.doi.org/10.1016/j.jep.2004.05.006] [PMID: 15261975]
[37]
Damasceno, D.C.; Netto, A.O.; Iessi, I.L.; Gallego, F.Q.; Corvino, S.B.; Dallaqua, B.; Sinzato, Y.K.; Bueno, A.; Calderon, I.M.P.; Rudge, M.V.C. Streptozotocin-induced diabetes models: Pathophysiological mechanisms and fetal outcomes. BioMed Res. Int., 2014, 2014, 819065.
[http://dx.doi.org/10.1155/2014/819065] [PMID: 24977161]
[http://dx.doi.org/10.1155/2014/819065] [PMID: 24977161]
[38]
Sreejesh, P.G.; Thampi, B.H.; Sreekumaran, E. Hypoglycaemic effect of glibenclamide: A critical study on the basis of creatinine and lipid peroxidation status of streptozotocin-induced diabetic rat. Indian J. Pharm. Sci., 2017, 79(5), 768-777.
[39]
Ighodaro, O.M.; Akinloye, O.A. Anti-diabetic potential of Sapium ellipticum (Hochst) Pax leaf extract in Streptozotocin(STZ)-induced diabetic Wistar rats. BMC Complement. Altern. Med., 2017, 17(1), 525.
[http://dx.doi.org/10.1186/s12906-017-2013-8] [PMID: 29216879]
[http://dx.doi.org/10.1186/s12906-017-2013-8] [PMID: 29216879]
[40]
Vats, V.; Yadav, S.P.; Grover, J.K. Effect of T. foenumgraecum on glycogen content of tissues and the key enzymes of carbohydrate metabolism. J. Ethnopharmacol., 2003, 85(2-3), 237-242.
[http://dx.doi.org/10.1016/S0378-8741(03)00022-9] [PMID: 12639747]
[http://dx.doi.org/10.1016/S0378-8741(03)00022-9] [PMID: 12639747]
[41]
Rodríguez, V.; Plavnik, L.; Tolosa de Talamoni, N. Naringin attenuates liver damage in streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2018, 105, 95-102.
[http://dx.doi.org/10.1016/j.biopha.2018.05.120] [PMID: 29852394]
[http://dx.doi.org/10.1016/j.biopha.2018.05.120] [PMID: 29852394]
[42]
Al Hroob, A.M.; Abukhalil, M.H.; Alghonmeen, R.D.; Mahmoud, A.M. Ginger alleviates hyperglycemia-induced oxidative stress, inflammation and apoptosis and protects rats against diabetic nephropathy. Biomed. Pharmacother., 2018, 106, 381-389.
[http://dx.doi.org/10.1016/j.biopha.2018.06.148] [PMID: 29966984]
[http://dx.doi.org/10.1016/j.biopha.2018.06.148] [PMID: 29966984]
[43]
Nabi, S.A.; Kasetti, R.B.; Sirasanagandla, S.; Tilak, T.K.; Kumar, M.V.J.; Rao, C.A. Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats. BMC Complement. Altern. Med., 2013, 13(1), 37.
[http://dx.doi.org/10.1186/1472-6882-13-37] [PMID: 23414307]
[http://dx.doi.org/10.1186/1472-6882-13-37] [PMID: 23414307]
[44]
Surya, S.; Arun Kumar, R.; Carla, B.; Sunil, C. Antihyperlipidemic effect of Ficus dalhousiae miq. stem bark on Triton WR-1339 and high fat diet-induced hyperlipidemic rats. Bull. Fac. Pharm. Cairo Univ., 2017, 55(1), 73-77.
[http://dx.doi.org/10.1016/j.bfopcu.2016.10.003]
[http://dx.doi.org/10.1016/j.bfopcu.2016.10.003]
[45]
Zarzecki, M.S.; Araujo, S.M.; Bortolotto, V.C.; de Paula, M.T.; Jesse, C.R.; Prigol, M. Hypolipidemic action of chrysin on Triton WR-1339-induced hyperlipidemia in female C57BL/6 mice. Toxicol. Rep., 2014, 1, 200-208.
[http://dx.doi.org/10.1016/j.toxrep.2014.02.003] [PMID: 28962239]
[http://dx.doi.org/10.1016/j.toxrep.2014.02.003] [PMID: 28962239]
[46]
de Souza, B.V.C.; Moreira Araújo, R.S.D.R.; Silva, O.A.; Faustino, L.C.; Gonçalves, M.F.B.; Dos Santos, M.L.; Souza, G.R.; Rocha, L.M.; Cardoso, M.L.S.; Nunes, L.C.C. Bauhinia forficata in the treatment of diabetes mellitus: A patent review. Expert Opin. Ther. Pat., 2018, 28(2), 129-138.
[PMID: 29168921]
[PMID: 29168921]
[47]
Harnafi, M.; Bekkouch, O.; Touiss, I.; Khatib, S.; Mokhtari, I.; Milenkovic, D.; Harnafi, H.; Amrani, S. Phenolic-rich extract from almond (Prunus dulcis) hulls improves lipid metabolism in triton WR-1339 and high-fat diet-induced hyperlipidemic mice and prevents lipoprotein oxidation: A comparison with fenofibrate and butylated hydroxyanisole. Prev. Nutr. Food Sci., 2020, 25(3), 254-262.
[http://dx.doi.org/10.3746/pnf.2020.25.3.254] [PMID: 33083374]
[http://dx.doi.org/10.3746/pnf.2020.25.3.254] [PMID: 33083374]
